Craniofacial Research Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA.
Bone. 2013 Sep;56(1):9-15. doi: 10.1016/j.bone.2013.04.022. Epub 2013 May 1.
Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity.
Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 μg/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed.
Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment.
We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible.
放射治疗会导致骨质血管严重减少。间歇性甲状旁腺激素（PTH）已被证明对成骨有合成代谢作用，但其对血管生成的影响尚不清楚。在本研究中，我们假设放射治疗会导致牵张再生骨的血管减少，而间歇性全身给予 PTH 会促进血管生成并逆转辐射引起的低血管化。
19 只 Lewis 大鼠分为三组。所有组均行左侧下颌骨牵张。两组在牵张前接受左侧下颌骨放射治疗，其中一组从牵张的第一天开始每天接受间歇性皮下 PTH（60 μg/kg）治疗，共 21 天。一组仅行下颌骨牵张，不接受放射治疗。在愈合期后，对大鼠进行微血管 CT 血管造影灌注和成像，并进行定量血管分析。
放射治疗导致牵张再生骨的骨质血管严重减少。在接受放射治疗的下颌骨进行牵张成骨术的情况下，间歇性 PTH 治疗导致血管容积分数、血管厚度、血管数量、各向异性程度显著增加，血管分离度显著降低（p<0.05）。接受放射治疗、接受 PTH 治疗和接受无放射治疗的牵张成骨术的两组之间，定量血管无明显差异。
我们定量证明放射治疗会导致骨质血管大量减少，间歇性给予 PTH 可逆转小鼠下颌骨牵张成骨术中的辐射诱导低血管化。虽然 PTH 诱导血管生成的确切机制尚待阐明，但本报告增加了间歇性 PTH 对骨形成的多效性作用的关键组成部分，并进一步支持了 PTH 增强辐射下颌骨骨再生的潜力。
